Viral Targeting with Knottins

Abstract

The use of targeting knottin polypeptides provides a means of selectively infecting target cells presenting species bound by the knottins. The targeted viruses may be used as cytotoxic agents, for example, as oncolytic viral therapeutics. Alternatively, the knottin-targeted viruses may be used to transform target cells in a gene therapy or immunotherapy context. An effective retargeted measles virus directed to integrins is demonstrated.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of priority to U.S. Provisional Application Ser. No. 62 / 408,735 entitled “Viral targeting with knottins,” filed Oct. 15, 2016, the contents which are hereby incorporated by reference.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0002]This invention was made with government support under grant no. CA097257, awarded by the National Institutes of Health. The government has certain rights in the invention.REFERENCE TO SEQUENCE LISTING, A TABLE, OR A COMPUTER PROGRAM LISTING COMPACT DISK APPENDIX[0003]This application is submitted with a computer readable sequence listing, submitted herewith via EFS as the ASCII text file named: “UCSF036NP_SL.txt”, file size approximately 9,903 bytes, created on Oct. 12, 2017 and hereby incorporated by reference in its entirety.BACKGROUND OF THE INVENTION[0004]There is an ongoing effort to develop engineered viruses to ablate tumors or deliver genes. Howeve...

AI Technical Summary

Benefits of technology

The patent is about using a new type of protein called cysteine knot, or knottin, to create better viruses for treating cancer and delivering genes to cells. These viruses can infect cells more efficiently and specifically, which makes them better for treating cancer and gene therapy. The use of knottins allows for targeted infection of specific cell types while minimizing infection of other cells.

Problems solved by technology

However, to date, the efficacy of such engineered viruses has been suboptimal.

Effective viral infection of target cells has been limited by low infection rates and / or undesirable infection of non-target cells.

However, the production of such viruses has proven laborious, as the receptor binding motif used to target the virus is typically a single chain antibody.

Antibodies suffer from significant practical limitations, including expensive and complicated recombinant production, poor penetration of solid tumors, and the difficulty of site-specifically incorporating modifications.

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